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To determine the effects of silica dust inhalation on the immunological defense mechanisms which are involved in pulmonary resistance to infection, mice were housed in exposure chambers and subjected to various concentrations of silica dust for various lengths of time; control mice were similarly housed without exposure to silica dust. These exposures were followed by examination of a variety of immunologic responses and morphological studies of tissue. There was a very severe reduction in the numbers of antibody forming cells in spleens and mediastinal lymph nodes after aerosol administration of antigens. There was decreased phagocytic activity of lung macrophages and decreased lung clearance of inhaled bacteria. There was a decrease in the antigen processing ability of lung derived macrophages, and a decreased response to antigens of spleen cells from silica exposed animals used to repopulate gamma irradiated syngenetic recipients. There were progressive cellular changes into the lungs including early infiltration of chronic inflammatory cells, followed by the development of silica containing macrophages, and after 39 weeks of exposure, the presence of silica associated fibrotic nodules both in the lungs and in the mediastinal lymph nodes. It is concluded that mice exposed in the manner serve as excellent models for further study of pathogenesis of diseases caused by inhalation of other toxic substances besides silica.